The aim of this study is to improve the molecular analysis of pre- neoplastic and neoplastic tissue obtained by endoscopic biopsy. The long- term goal of this study is to develop a method of performing molecular analysis of lesions from which only limited sized specimens can be sampled. Endoscopic biopsies are routinely obtained from gastrointestinal neoplasms but two major problems have prevented their utilization for molecular analysis. The primary problem with existing technology has been the need to rely solely on visual inspection to determine which tissue can be used for molecular analysis. The second is the inability to perform genetic testing on the small size of tissue specimens that are obtained from endoscopic biopsies. This proposal will assess the ability of two techniques to improve the detection of mutations in neoplastic tissues using endoscopic biopsy material. The first technique is an "optical biopsy" using laser induced fluorescence (LIF) and diffuse reflectance spectroscopy that allows the selection the appropriate neoplastic tissue for analysis. This device allows immediate localization of the neoplastic tissue with a high level of accuracy, which permits the sampling of the most appropriate tissue for molecular analysis. The samples will be processed using a new technique termed Denaturing High Pressured Liquid Chromatography (DHPLC) which is a rapid, sensitive, and automated technique for screening genetic abnormalities. We would propose to test these techniques in Barrett's esophagus, a pre-malignant epithelial tissue of the distal esophagus. These patients have common well-characterized molecular abnormalities that can be examined with these techniques. We will compare the rests of molecular analysis of tissue obtained with optical biopsy compared with obtained with standard techniques. In addition, we will assess the ability of DHPLC followed by direct gene sequencing to rapidly screen and identify mutations. It is anticipated that the combination of these techniques can substantially increase the ability to detect molecular abnormalities from limited tissue samples obtained through endoscopy. These techniques have the potential to advance the molecular analysis of any tissue samples of limited size.